Concorde TrialDate: April 1, 1993
Source: National Institutes of Health (NIH)
Author: National Institute of Allergy and Infectious Diseases (NIAID)
In a letter in the April 3 Lancet, investigators report initial results of a joint Anglo-French study, the Concorde trial, that assessed the benefits of the drug zidovudine (AZT) in HIV-infected individuals without symptoms. The authors report that after three years of follow-up, they saw no differences in the cumulative risk of death or disease progression between HIV-infected individuals given immediate AZT therapy and those who were not treated until they developed decreases in the numbers of certain immune system cells or at the time that AIDS-related symptoms occurred.
Daniel F. Hoth, M.D., director of the Division of AIDS at the National Institute of Allergy and Infectious Diseases (NIAID), says, "The Lancet letter is based on a preliminary analysis, with many important details to be clarified. We look forward to meeting with our European colleagues and reviewing this data in detail. However, at this time we see no basis for changing the current recommendation to initiate antiretroviral therapy for HIV-infected persons whose CD4+ T cell count falls below 500 per cubic millimeter(mm3) of blood." CD4+ T cells are the crucial immune system cells depleted during HIV infection. A healthy, uninfected individual usually has 800 to 1200 CD4+ T cells/mm3.
The Lancet authors report that while their findings are "not inconsistent" with findings of previous studies at comparable follow-up times, the delay in progression to AIDS or ARC seen in previous studies "was not seen over the longer follow-up period."
Four previously-published placebo-controlled trials, with a median follow-up period of one year, have found that early treatment with AZT in certain patients with early or no HIV-related symptoms can delay the onset of severe disease. The largest of these, the NIAID-sponsored AIDS Clinical Trials Group (ACTG) 019, found that AZT delayed the onset of advanced AIDS related complex (ARC) and AIDS for individuals who entered the study with CD4+ T cell counts of 500/mm3 or less.
Paul Volberding, M.D., principal investigator of ACTG 019 and director of the AIDS Program at San Francisco General Hospital, says, "It is increasingly apparent AZT is a drug with benefits that are limited in duration, particularly in patients with more advanced disease. While we know that AZT can help patients in the short term, the real focus of AIDS clinical research today is on developing other treatment strategies, such as sequential or combination therapies, that are effective and well-tolerated over extended periods of time."
A state-of-the-art conference on the optimal use of antiretrovirals, sponsored by NIAID, will be held this summer in Bethesda, MD.
The Office of Communications National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda, MD 20892
Public Health Service U.S. Department of Health and Human Services